Physiology and pathophysiology of vascular signaling controlled by cyclic guanosine 3′, 5′-cyclic monophosphate–dependent protein kinase

T Münzel, R Feil, A Mülsch, SM Lohmann… - Circulation, 2003 - Am Heart Assoc
T Münzel, R Feil, A Mülsch, SM Lohmann, F Hofmann, U Walter
Circulation, 2003Am Heart Assoc
defects, desensitization, or other aberrations in the pathways distal to NO/NPs must be
recognized as capable of derailing the desired procession of events. The ensuing
discussion illustrates that understanding the complex array of interactions beyond NO/NPs is
a serious challenge and an integral aspect of achieving insights into successful strategies
for opposing cardiovascular disease. cGMP Effectors The cGMP signal is diversified through
cell type–specific collections of intracellular cGMP receptors. In the cardiovascular system …
defects, desensitization, or other aberrations in the pathways distal to NO/NPs must be recognized as capable of derailing the desired procession of events. The ensuing discussion illustrates that understanding the complex array of interactions beyond NO/NPs is a serious challenge and an integral aspect of achieving insights into successful strategies for opposing cardiovascular disease. cGMP Effectors
The cGMP signal is diversified through cell type–specific collections of intracellular cGMP receptors. In the cardiovascular system, the major cGMP effectors are cGMP-regulated phosphodiesterases (PDEs) 9, 10 and cGKs (see subsequently in this article). 11–14 Cyclic nucleotide PDEs hydrolyze cAMP and/or cGMP and thus terminate their action. They are presently classified as PDE families 1 through 11, encoded by 20 genes, generating more than 50 PDE isozymes. 14a cGMP-hydrolyzing PDEs include ones that specifically (PDE 5, 6, and 9) or preferentially (PDE 1A1) hydrolyze cGMP, 15 as well as ones that hydrolyze both cGMP and cAMP (PDE 1 to 3 and 10 to 11). 9, 10, 16 cGMP may also be transported out of cells by the multidrug-resistant protein 5. 17 The activity of certain PDEs can be stimulated (PDE 2) or inhibited (PDE 3) by cGMP. Also, cGKI phosphorylates and activates PDE 5 to rapidly terminate cGMP action. 18, 19 Platelets contain at least PDE 2, 3, and 519, 20; arterial VSM cells at least PDE 1 to 5; and venous VSM cells at least PDE 1, 4, and 5. 21
Am Heart Assoc